Monocyte chemoattractant protein-1 and large artery structure and function in young individuals : the African-PREDICT study

Abstract

Motivation - In sub-Saharan Africa, the burden of cardiovascular diseases (CVD) is increasing at an alarming rate. This may be due to the rapid urbanisation of traditional black populations, leading to lifestyle changes (i.e. unhealthy diet, increased access to alcohol and a more sedentary lifestyle), which may increase their vulnerability to cardiovascular changes, such as hypertension, increased arterial stiffness and atherosclerosis. These changes in lifestyle can however not comprehensively account for the differences seen in cardiovascular disease development and progression between black and white populations. Black populations present with present with impaired vascular and endothelial function, as witnessed by greater hypertension and arterial stiffness, when compared to their white counterparts. The impaired endothelial function and differences in arterial function seen in black individuals may increase their vulnerability for cardiovascular disease. In hypertension and established CVD the plasma levels of C-reactive protein and proinflammatory cytokines, as well as the chemokines, are all increased. The link between endothelial dysfunction, the inflammatory activation of the endothelium and the development of hypertension and ultimately CVD are well established. In the black population, not only blood pressure, but inflammatory markers are higher when compared to whites. Thus understanding the role of inflammation in the pathogenesis of arterial stiffness, hypertension and CVD is of great importance for future development of treatment strategies and individual risk assessment. In cardiovascular disease investigation the role of the chemokines and especially monocyte chemoattractant protein-1 and how it relates to an increased risk for hypertension and CVD are enjoying increasing attention. Chemoattractant proteins are part of the larger family of chemokines that direct the migration of monocytes from the blood to sites of inflammation. This arrest and transmigration of monocytes from the circulation by MCP-1 is induced under conditions of physiological shear force and by the pro-inflammatory cascade. MCP-1 is involved in the development of atherosclerosis through its promotion of the accumulation of lipids in the sub-endothelial intimal layer, as well as the differentiation of monocytes to macrophages and foam cells. MCP-1 correlates with carotid wall thickness, as is associated with hypertension and an increased risk of myocardial infarction, sudden death, coronary angioplasty and stent restenosis. The pathological influence of MCP-1 in cardiovascular disease was however shown in largely elderly, white populations and little is known about MCP-1 levels in young, seemingly healthy black and white individuals, and how it may influence the development of cardiovascular disease risk and progression. This study will herefore attempt to demonstrate ethnic differences and plasma MCP-1 levels, and how it may play an important role in the early detection of vascular dysfunction and disease development in the South African population. Aim - The central aim of this study was to determine whether MCP-1, as possible early marker of endothelial dysfunction, is associated with arterial stiffness and cIMT in young black and white individuals participating in the African-PREDICT study. Methodology - This sub-study form part of the African-PREDICT study. We investigated 403 apparently healthy individuals aged 20-30 years, consisting of black (N=198) and white (N=205) men and women. Hypertensive individuals were excluded from the study. The study was reviewed by the Health Research and Ethics Committee (HREC) of the North-West University (Potchefstroom campus) and all participants signed informed consent prior to their enrolment in the study. Trained field workers gathered demographical data in the form of questionnaires and where necessary it was done in the participant’s home language. Anthropometric measurements were taken, with calibrated instruments and included body weight, height, waist circumference, while body mass index was calculated as kg/m². Duplicate office brachial blood pressure measurement was taken on the left and right arm, with a 5 minute interval. Participants were fitted with a validated 24-hour ambulatory blood pressure apparatus. Carotid-femoral pulse wave velocity (cfPWV) were measured along the descending thoracic-abdominal aorta, suing the foot-to-foot velocity method, and central systolic blood pressure (SBP) were derived from the pulse wave analyses. B-mode ultrasonography was used to measure carotid intima-media thickness (cIMT). Plasma MCP-1 was determined using the quantitative sandwich enzyme immunoassay technique. Furthermore serum intercellular adhesion molecules (ICAM) and vascular cell adhesion molecule (VCAM), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) were measured. Results - cfPWV and cIMT were similar between the black and white groups, but black men and women showed higher central SBP and higher MCP-1 levels (both p<0.001) than their white counterparts. In addition, black women showed higher brachial SBP (p<0.001) and higher mean arterial pressure (p=0.001) than white women. We found a consistent positive association only in black women between cIMT and MCP-1 in single, partial and multiple regression analyses (R²=0.151; β=0.248 [0.14; 0.35]; p=0.021). Conclusion - In a young healthy bi-ethnic population, we found elevated central SBP and MCP-1 in blacks. In black women carotid wall thickness was related to early endothelial dysfunction (MCP-1), which may indicate an increased risk for early vascular deterioration in young black individuals.